Synthesis of (−)‐Deoxynupharidine by Allenic Hydroxylamine Cyclisation

Abstract

(À)-Deoxynupharidine has been synthesised via an intermediate that can also be used for other Nuphar alkaloids. Significants teps include the optimisede nzymatic resolution of an allenic alcohol, highly diastereoselective silvercatalysed cyclisation of an allenic hydroxylamine, selective cross-metathesis,d iastereoselectivei ntramolecular reductive amination,a nd stereoelectronically controlled enolate alkylation.

Chromatography with silver nitrate: part 2

“…In a similar vein Bates et al 108 utilised SNIS as part of an optimisation study into the cyclisation of allene 247 into the trans-isoxazolidine 248. However, it did not outperform silver triflate in terms of yield and selectivity (Scheme 53).…”

The role of biocatalysis in the asymmetric synthesis of alkaloids – an update

“…In the rst of these studies, the allenic benzoate ester 24 (Scheme 4a) was enantioselectively hydrolysed by lipase PS 37 to obtain alcohol (S)-25 in 38% yield and 80% ee (E ¼ 15). 45 Transformation of the hydroxyl group into a Bocprotected hydroxylamine set the stage for a silver(I)-catalysed cyclisation that gave isoxazolidine 27 with excellent diastereoselectivity (22 : 1 dr). From this intermediate, (À)-deoxynupharidine (30) was prepared in nine steps, whereby the third chirality centre was formed with complete diastereocontrol in an intramolecular reductive amination reaction.…”

Studies on the synthesis of the lasubine alkaloids

“…We have noted the reluctance of δ-lactams to form previously. 14 In this instance, we employed the same solution as before: hydrolysis to the parent acid 29, followed by ring closure using EDCI. This yielded the desired lactam 30 which, on treatment with lithium aluminium hydride in THF at reflux, was converted into (+)-epilasubine-II 31 in quantitative yield.…”